ABCMdb

PMID: 26617691

Li R, Miao L, Qin L, Xiang Y, Zhang X, Peng H, Mailamuguli, Sun Y, Yao H
A meta-analysis of the associations between the Q141K and Q126X ABCG2 gene variants and gout risk.
Int J Clin Exp Pathol. 2015 Sep 1;8(9):9812-23. eCollection 2015., [PubMed]

Sentences

No. Mutations Sentence Comment

3 ABCG2 p.Gln141Lys ABCG2 p.Gln126* ABCG2 is a urate transporter, and the Q141K and Q126X variants of ABCG2 have been associated with a risk of developing gout, though previous studies of these associations have been inconsistent. Login to comment 5 ABCG2 p.Gln141Lys ABCG2 p.Gln126* In total, 9 eligible articles on the associations between the Q141K (rs2231142) and Q126X (rs72552713) variants and gout risk, including 11 case-control studies were selected. Login to comment 8 ABCG2 p.Gln141Lys The Q141K variant was found to significantly increase the risk of gout in Asians (dominant model: OR=2.64, 95% CI=2.04-3.43, P=0.02 for heterogeneity; recessive model: OR=3.19, 95% CI=2.56-3.97, P=0.28 for heterogeneity; co-dominant model: OR=1.37, 95% CI=1.18-1.59, P=0.09 for heterogeneity) and other populations (dominant model: OR=1.85, 95% CI=1.20-2.85, P<0.0001 for heterogeneity; recessive model: OR=3.78, 95% CI=2.28-6.27, P=0.19 for heterogeneity; co-dominant model: OR=1.48, 95% CI=1.26-1.74, P=0.19 for heterogeneity). Login to comment 9 ABCG2 p.Gln126* The Q126X variant also significantly increased the risk of gout in Asians (dominant model: OR=3.87, 95% CI=2.07-7.24, P=0.06 for heterogeneity). Login to comment 12 ABCG2 p.Gln141Lys ABCG2 p.Gln126* Keywords: Gout, Q141K, Q126X, single nucleotide polymorphism, meta-analysis Introduction Gout is a recurrent relapsing inflammatory disease, caused by the precipitation of monosodium urate (MSU) crystals in the joints and soft tissues. Login to comment 26 ABCG2 p.Gln141Lys ABCG2 p.Gln126* Among these, Q141K and Q126X are the most commonly studied. Login to comment 27 ABCG2 p.Gln141Lys SNP rs2231142, also referred to as C421A or Q141K in ABCG2, is located in exon 5 [10] and substitutes glutamic acid for diaminocaproic acid. Login to comment 29 ABCG2 p.Gln126* SNP rs72552713, also referred to as C376T or Q126X in ABCG2, has also been shown to play a role in gout. Login to comment 33 ABCG2 p.Gln141Lys ABCG2 p.Gln126* The literature search was performed in English and Chinese using the following primary key words: gout, ABCG2, C421A, Q141K, rs2231142, C376T, Q126X, and rs72552713. Login to comment 37 ABCG2 p.Gln141Lys Characteristics of the included studies (Q141K) First author (Ref.) Year Ethnicity/country Diagnostic standard Study design Sample size (case/control) HWE p-value Genotype distribution (case/control) Genotype frequency (case/control) CC CA AA CC (%) CA (%) AA (%) Wang Qiong [17] 2014 Asians China ACR preliminary diagnostic criteria for acute gout (1977) Case-control 185/311 Yes 64/157 86/126 35/28 34.6/50.5 46.5/40.5 18.9/9.0 Zhang Xin-Lei [28] 2014 Asians China ACR preliminary diagnostic criteria for acute gout (1977) Case-control 147/321 Yes 30/167 79/134 38/20 20.4/52.0 53.7/41.7 25.9/6.2 Li Fa-Gui [12] 2011 Asians China ACR preliminary diagnostic criteria for acute gout (1977) Case-control 200/235 Yes 64/103 91/112 45/20 32.0/43.8 45.5/47.7 22.5/8.5 Amanda 1 [25] 2010 Maori New Zealand ACR preliminary diagnostic criteria for acute gout (1977) Case-control 185/215 Yes 142/172 34/39 2/1 79.8/81.1 19.1/18.4 1.1/0.5 Amanda 2 [25] 2010 Pacific Islander New Zealand ACR preliminary diagnostic criteria for acute gout (1977) Case-control 173/109 Yes 58/69 78/36 37/4 33.5/63.3 45.1/33.0 21.4/3.7 Amanda 3 [25] 2010 Caucasian New Zealand ACR preliminary diagnostic criteria for acute gout (1977) Case-control 214/562 Yes 122/425 76/125 13/8 57.8/76.2 36.0/22.4 6.2/1.4 Danqiu Zhou [36] 2014 Asians China ACR preliminary diagnostic criteria for acute gout (1977) Case-control 352/350 Yes 87/167 181/150 84/33 24.7/47.7 51.4/42.9 23.9/9.4 Klaus [32] 2009 Caucasian German ACR preliminary diagnostic criteria for acute gout (1977) Case-control 677/1552 Yes 500/1241 168/299 9/12 73.9/80.0 24.8/19.2 1.3/0.8 Zhang Xiu-Juan [36] 2012 Asians China ARA diagnostic criteria for acute gout (1997) Case-control 110/236 Yes 35/120 55/96 20/20 31.8/50.8 50.0/40.7 18.2/8.5 You Yu-Quan [39] 2013 Asians China ACR preliminary diagnostic criteria for acute gout (1977) Case-control 154/160 Yes 48/98 78/49 28/13 31.2/60.3 50.6/30.6 18.2/8.1 Ye De-Shao [62] 2012 Asians China ACR preliminary diagnostic criteria for acute gout (1977) Case-control 102/102 Yes 23/53 42/40 37/9 22.5/52.0 41.2/39.2 36.3/8.8 Table 2. Login to comment 38 ABCG2 p.Gln141Lys ABCG2 p.Gln126* ABCG2 p.Gln126* Characteristics of the included studies (Q126X) First author (Ref.) Year Ethnicity/ country Diagnostic standard Study design Sample size (case/control) HWE p-value Genotype distribution (case/control) Genotype frequency (case/control) CC CT TT CC (%) CT (%) TT (%) Zhang Xin-Lei [28] 2014 Asians China ACR preliminary diagnostic criteria for acute gout (1977) Case-control 136/321 Yes 127/320 9/1 0/0 93.4/99.7 6.6/0.3 0/0 Danqiu Zhou [36] 2014 Asians China ACR preliminary diagnostic criteria for acute gout (1977) Case-control 352/350 Yes 319/338 33/12 0/0 90.6/96.6 9.4/3.4 0/0 The following index terms were used: gout and ABCG2, gout and C421A, gout and Q141K, gout and rs2231142, gout and C376T, gout and Q126X, and gout and rs72552713. Login to comment 39 ABCG2 p.Gln141Lys Selection criteria In this meta-analysis, we established the following inclusion criteria: (1) the publication Figure 2. Forest plot of the associations between the Q141K variant and gout risk using the A: Dominant model (CC compared to AC+AA), B: Recessive model (AA compared to CC+AC), and C: Co-dominant model (AC compared to CC+AA). Login to comment 40 ABCG2 p.Gln141Lys Figure 3. Forest plot describing ethnicity in the dominant model (Q141K). Login to comment 48 ABCG2 p.Gln141Lys Fortunately, the quality of the included studies was high, and we were able to collect the following data from each study: the first author`s name, publication year, country, ethnicity, diagnostic standard of gout, study design, total number of cases and controls, HWE P-value, genotype distribution and geno- Figure 4. Forest plot describing ethnicity in the recessive model (Q141K). Login to comment 53 ABCG2 p.Gln141Lys ABCG2 p.Gln141Lys ABCG2 p.Gln141Lys ABCG2 p.Gln126* Each relationship was assessed in a dominant model (Q141K: CC compared to AC+AA; Q126X: CC compared to CT+TT), a recessive model (Q141K: AA compared to CC+AC), and a co-dominant model (Q141K: AC compared to CC+AA). Login to comment 59 ABCG2 p.Gln141Lys Figure 5. Forest plot describing ethnicity in the co-dominant model (Q141K). Login to comment 66 ABCG2 p.Gln141Lys ABCG2 p.Gln126* All of these 9 studies involved the Q141K variant, and only 2 studies referred to the Q126X variant. Login to comment 68 ABCG2 p.Gln141Lys Of these 9 studies, of the Q141K variant, one study contained data for three different ethnicities; therefore, each of these studies was treated separately. Login to comment 72 ABCG2 p.Gln126* We extracted the characteristics of these studies, which are summarized in Tables 1, 2 of Article 9 on the Q126X variant. Login to comment 75 ABCG2 p.Gln126* Subgroup analysis by ethnicity also revealed significant associations for both Asians (dominant model: OR=2.64, 95% CI=2.043.43, P=0.02 for heterogeneity; recessive model: OR=3.19, 95% CI=2.56-3.97, P=0.28 for heterogeneity; co-dominant model: OR=1.37, 95% CI=1.181.59, P=0.09 for heterogeneity) and other populations (dominant model: OR=1.85, Figure 6. Forest plot for the association between the Q126X variant and gout risk using the dominant model (CT+TT compared to CC). Login to comment 77 ABCG2 p.Gln141Lys Sensitivity analysis for the association between the Q141K variant and gout risk. Login to comment 79 ABCG2 p.Gln141Lys Begg`s funnel plot examining the publication bias of studies using the recessive model (Q141K). Login to comment 87 ABCG2 p.Gln141Lys ABCG2 p.Gln126* Among the ABCG2 polymorphisms, Q141K and Q126X are the most commonly studied. Login to comment 88 ABCG2 p.Gln141Lys ABCG2 p.Gln126* Nevertheless, the role of the Q141K variant in gout risk and the potential for the Q126X variant to increase gout risk are controversial. Login to comment 90 ABCG2 p.Gln141Lys Hirotaka et al. [25], Kazumasa et al. [11] and Xiaofei Lv [26] also showed that the Q141K variant increases the risk of gout. Login to comment 92 ABCG2 p.Gln126* Until now, there has been no meta-analysis demonstrating the role of Q126X in gout. Login to comment 95 ABCG2 p.Gln141Lys ABCG2 p.Gln126* Our results suggested that the Q141K variant results in increased gout risk in dominant, recessive, and co-dominant models, and in subgroup analyses, Q126X also increased gout risk in a dominant model. Login to comment 101 ABCG2 p.Gln141Lys Ethnic differences are always mentioned by researchers not only in discussions of gout [29] but also in the association between the Q141K polymorphism and gout risk [24, 30]. Login to comment 103 ABCG2 p.Gln141Lys From this subgroup analysis, we found that regardless of race, the Q141K variant increases the risk of gout. Login to comment 118 ABCG2 p.Gln141Lys ABCG2 p.Gln126* Our evidence revealed that Q141K and Q126X are risk factors for the development of gout. Login to comment 182 ABCG2 p.Gln141Lys Association of functional polymorphism rs2231142 (Q141K) in the ABCG2 gene with serum uric acid and gout in 4 US populations. Login to comment 195 ABCG2 p.Gln141Lys Association between ABCG2 Q141K polymorphism and gout risk affected by ethnicity and gender: a systematic review and meta-analysis. Login to comment